Warfarin is the most common oral anticoagulant. Because of a narrow therapeutic range, interindividual differences in drug responses, and the risk of bleeding, there are many challenges in using warfarin. We need to predict the warfarin maintenance dose. However, ethnic-specific algorithms may be required, and some Chinese algorithms do not perform adequately. Therefore, we aimed to establish a Han Chinese appropriate algorithm.We recruited a study group consisting of 361 Han Chinese patients receiving warfarin treatment who had heart valve replacements. Genotyping of 38 single nucleotide polymorphisms (SNPs) in 13 candidate genes was carried out using the MassARRAY. In the derivation cohort, a multiple linear regression model was constructed to predict the warfarin dosage. We evaluated the accuracy of our algorithm in the validation cohort and compared it with the other 5 algorithms based on Han Chinese and other races.We established a Han Chinese-specific pharmacogenetic-guided warfarin dosing algorithm. Warfarin maintenance dosage (mg/day) = 1.787 − 0.023 × (Age) + 1.151 × (BSA [m2]) + 0.917 × (VKORC1 AG) + 4.619 × (VKORC1 GG) + 0.595 × (CYP4F2 TT) + 0.707 × (CYP2C19 CC). It explained 58.3% of the variance in warfarin doses in Han Chinese patients and was superior to the other 5 algorithms. The ability of the 6 algorithms which estimate the required dose correctly was tested. Our model had a mean absolute error of 0.74 mg/day, the other 5 models have mean absolute error of 0.81 mg/day,1.05 mg/day, 1.24 mg/day, 1.18 mg/day, and 0.85 mg/day, respectively. Our model had a mean percentage error of 26.9%, the other 5 models have the mean percentage error of 27.7%, 27.2%, 52.3%, 45.7%, and 29.3%, respectively.Physicians can not adopt algorithm from other race directly to predict warfarin dose in patients with heart valve replacements, they should establish a new algorithm or adjust another algorithm to fit their patients. The algorithm established in this study has the potential to assist physicians in determining warfarin doses that are close to the appropriate doses.
performed segmentectomy for compromised patients, and patients with small-sized NSCLC and adequate pulmonary function for curative intent. The aim of this study was to investigate first recurrence sites and risk factors of recurrence in NSCLC patients who underwent segmentectomy. Method: We retrospectively reviewed 136 patients with clinical stage I NSCLC (the 7th edition of the TNM classification) who underwent segmentectomy at Niigata University Medical and Dental Hospital between 2000 and 2016. We investigated first recurrence site to classify as intrathoracic or extrathoracic recurrence. The significant demographic, clinical, and pathologic factors identified with the log rank test in univariate analyses were analyzed with the Cox proportional hazards regression model to examine independent predictors for recurrence in multivariate analysis. For the significant predictor, we determined optimal cutoff points by receiver operating characteristic (ROC) analysis and Youden's Index Result: Of the 136 patients in this study, 81 were male and 55 were female, and the median age was 71 years (range, 41 to 86 years). During the median follow-up period of 1568 days (range, 15 to 6584 days), recurrence was developed in 11 patients. Intrathoracic recurrence was developed only in 4 patients, including 2 patients with surgical resection margin recurrence. The 5-and 10-year recurrence-free probabilities were 89.7% and 89.7%, respectively. Solid tumor component size on computed tomography (CT) was identified as an independent significant predictor (hazard ratio [HR], 3.459). To illustrate ROC curve and use Youden's Index, the optimal cutoff points were determined as 1.5 cm for solid component size on CT. Conclusion: In the study, the NSCLC patients with solid component of larger than 1.5 cm on CT had a higher risk for postoperative recurrence after segmentectomy. However it is still unknown whether these patients could be cured by lobectomy, because many of the patients with postoperative recurrence had extrathoracic recurrence.
genes expressed by the paternal allele are required for proper placentation and organogenesis; while the expression of non-coding genes encoded by the maternal allele were found to be temporally active in the brain. Previous reports identified few miRNAs at the locus that were able to stratify low and high risk patients with non-small cell lung carcinoma (NSCLC). However, a locus-wide analysis of miRNA deregulation across smokingassociated tumors still remains unexplored. To address this, we quantified the expression of 51 miRNAs in 10 smoking-associated cancer types and assessed their differential expression in unpaired normal and malignant tissues. Method: We analyzed the small RNA transcriptome in 10 cancer types from The Cancer Genome Atlas (TCGA) clinical cohorts (i.e. LUAD, LUSC, HNSC, kidney, stomach, esophagus, bladder, cervical, pancreas and liver). All small RNA sequencing reads were aligned on the human genome build 19 (hg19) and normalized using our in-house bioinformatics pipeline. miRNAs with expressions greater than or equal to 1.0 RPM in 10 percent of samples were included for further analysis. Zetascore values were calculated and used for unsupervised hierarchical clustering to identify distinct patterns of deregulation across different cancer types. We validated our findings using 132 paired NSCLC samples from the British Columbia Cancer Agency (BCCA). Small RNA sequencing of the validation cohort was performed using Illumina Hi-seq 2000 platform. All samples were microdissected prior to RNA isolation. Result: We identified 39 miRNAs that are expressed in all cancer types included in this study. Unsupervised hierarchical clustering based on miRNA z-score values revealed a distinct pattern of deregulation in NSCLC compared to other smoking-associated malignancies. Many of these miRNAs were upregulated in both lung adenocarcinoma and squamous carcinoma while other cancers showed either repression or unchanged expression. We further assessed the expression of these miRNAs in metastatic (with lymph node/distant organ invasion) and non-metastatic lung adenocarcinoma (LUAD) cases using TCGA and BCCA clinical cohorts. From this analysis, we found miR-323b, miR-433 and miR-889 consistently unregulated (p value 0.01) in metastatic tumors. Conclusion: NSCLC tumors showed a unique pattern of deregulation in chromosome 14q32 small non-coding genes when compared with other smoking-associated malignancies. Also, we identified three miRNAs that were significantly upregulated in metastatic LUAD cases. Target prediction and thorough functional assays of these miRNAs may reveal novel pathways disrupted during the metastatic progression of LUAD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.